更新于：2024-06-24
Demcizumab
更新于：2024-06-24
概要
基本信息
在研机构- |
最高研发阶段终止临床2期 |
首次获批日期- |
最高研发阶段(中国)- |
特殊审评孤儿药 (美国) |
序列信息
Sequence Code 9976311H
来源: *****
Sequence Code 319372683L
来源: *****
关联
11
项与 Demcizumab 相关的临床试验A Phase 1b, Open-Label, Dose Escalation and Expansion Study of Demcizumab Plus Pembrolizumab in Patients With Locally Advanced or Metastatic Solid Tumors
A 3-Arm Phase 2 Double-Blind Randomized Study of Carboplatin, Pemetrexed Plus Placebo versus Carboplatin, Pemetrexed plus 1 or 2 Truncated Courses of Demcizumab in Subjects with Non-Squamous Non-Small Cell Lung Cancer - DENALI
A 3-Arm Phase 2 Double-Blind Randomized Study of Gemcitabine, Abraxane® Plus Placebo Versus Gemcitabine, Abraxane® Plus 1 or 2 Truncated Courses of Demcizumab in Subjects With 1st-Line Metastatic Pancreatic Ductal Adenocarcinoma
100 项与 Demcizumab 相关的临床结果
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100 项与 Demcizumab 相关的转化医学
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100 项与 Demcizumab 相关的专利（医药）
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8
项与 Demcizumab 相关的文献（医药）2021-01-01Theranostics1区 · 医学
Spleen plays a major role in DLL4-driven acute T-cell lymphoblastic leukemia
1区 · 医学
ArticleOA
作者: Aifantis, Iannis ; Herranz, Daniel ; Singh, Amartya ; Lira, Sergio A ; Indraccolo, Stefano ; Shen, Shiqian ; Trimarchi, Thomas ; Xiong, Huizhong ; Minuzzo, Sonia ; Parkhurst, Christopher N ; Lobry, Camille ; Brengues, Muriel ; Maraver, Antonio ; Khiabanian, Hossein ; Garambois, Veronique ; Gómez-López, Gonzalo ; Gobert, Michael ; Tadokoro, Carlos E ; Lafaille, Juan J ; Mancini, Maicol ; Furtado, Glaucia C
The Notch pathway is highly active in almost all patients with T-cell acute lymphoblastic leukemia (T-ALL), but the implication of Notch ligands in T-ALL remains underexplored. Methods: We used a genetic mouse model of Notch ligand delta like 4 (DLL4)-driven T-ALL and performed thymectomies and splenectomies in those animals. We also used several patient-derived T-ALL (PDTALL) models, including one with DLL4 expression on the membrane and we treated PDTALL cells in vitro and in vivo with demcizumab, a blocking antibody against human DLL4 currently being tested in clinical trials in patients with solid cancer. Results: We show that surgical removal of the spleen abrogated T-ALL development in our preclinical DLL4-driven T-ALL mouse model. Mechanistically, we found that the spleen, and not the thymus, promoted the accumulation of circulating CD4+CD8+ T cells before T-ALL onset, suggesting that DLL4-driven T-ALL derives from these cells. Then, we identified a small subset of T-ALL patients showing higher levels of DLL4 expression. Moreover, in mice xenografted with a DLL4-positive PDTALL model, treatment with demcizumab had the same therapeutic effect as global Notch pathway inhibition using the potent γ-secretase inhibitor dibenzazepine. This result demonstrates that, in this PDTALL model, Notch pathway activity depends on DLL4 signaling, thus validating our preclinical mouse model. Conclusion: DLL4 expression in human leukemic cells can be a source of Notch activity in T-ALL, and the spleen plays a major role in a genetic mouse model of DLL4-driven T-ALL.
2020-12-01Annals of translational medicine4区 · 医学
NOTCH signalling in ovarian cancer angiogenesis
4区 · 医学
Review
作者: Samartzis, Eleftherios Pierre ; Boussios, Stergios ; Ortega, Belen ; Simon, Soraya ; Perez-Fidalgo, Jose Alejandro
The Notch signalling pathway is involved in the new vessel formation process by regulating tip and stalk cells, which are key cells in the sprout formation. This process is essential in both normal ovary and cancer angiogenesis and is regulated by Notch-VEGF crosstalk. Furthermore, Notch has been linked in ovary with stem cell maintenance and epithelial mesenchymal transition processes. Dysregulation of the Notch pathway is frequent in ovarian cancer (OC) and it has been associated with impaired survival and advanced stages or lymph node involvement. Notch also plays a role in chemoresistance to platinum. In this context, this pathway has emerged as an attractive target for precision medicine in OC. Two main targets of this pathway concentrate the clinical development of compounds blocking Notch: gamma secretase and Delta-like ligand 4. Most of the clinical trials including OC patients have been developed in phase I or phase Ib. Despite being in an early phase, both of these compounds, navicixizumab or demcizumab, two monoclonal antibodies targeting Dll4, showed promising efficacy data in platinum-resistant OC patients in recent studies. This review will focus on the mechanisms of the Notch pathway with special interest in angiogenesis regulation and the implication of Notch as a potential therapeutic target in OC.
2020-05-01Gynecologic oncology2区 · 医学
Demcizumab combined with paclitaxel for platinum-resistant ovarian, primary peritoneal, and fallopian tube cancer: The SIERRA open-label phase Ib trial
2区 · 医学
Article
作者: Anil K. Sood ; Robert Stagg ; Katelyn F. Handley ; Robert L. Coleman ; Robert Burger ; Kathleen N. Moore ; Graziela Zibetti Dal Molin
OBJECTIVES:
To evaluate the safety and preliminary efficacy of demcizumab (DLL4 targeted IgG2 humanized monoclonal antibody; potent inhibitor of the Notch pathway) in combination with weekly paclitaxel in platinum-resistant epithelial ovarian cancer (EOC); and to determine the maximum tolerated dose (MTD) or maximum administered dose (MAD).
METHODS:
We conducted a 3 + 3 dose-escalation trial in patients with recurrent, platinum-resistant EOC with RECIST v. 1.1 measurable disease and ≤4 prior chemotherapy regimens. Two dosing cohorts (2.5 mg/kg and 5 mg/kg) were targeted; however, an intermediate dose level (3.5 mg/kg) was to be evaluated if the 5 mg/kg dose was not tolerable. Demcizumab was administered on days 1 and 15 and paclitaxel, weekly on days 1, 8, and 15 for each of three 28-day cycles: the 3-cycle doublet could be repeated once if safe. Thereafter, paclitaxel was administered until unacceptable toxicity or disease progression.
RESULTS:
Nineteen patients were enrolled. No dose-limiting toxicities (DLT) were observed; however, the intermediate dose level (3.5 mg/kg) was enrolled and expanded based on emerging safety data from other trials in the demcizumab program. The MTD was not reached. The most common treatment emergent adverse events (TEAE) were diarrhea (68%), fatigue (58%), peripheral edema (53%), and nausea (53%). Pulmonary hypertension, grade 2 (n = 2) and grade 1 (n = 1), was observed. Overall response rate (ORR) was 21% (95% CI: 6-45%); clinical benefit rate (CBR) was 42% (95% CI: 20-66%).
CONCLUSIONS:
Demcizumab in combination with paclitaxel has a manageable toxicity profile and showed activity in patients with heavily pretreated platinum-resistant ovarian cancer.
100 项与 Demcizumab 相关的药物交易
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外链
| KEGG | Wiki | ATC | Drug Bank |
|---|---|---|---|
| D10353 | Demcizumab | - |
研发状态
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| 适应症 | 最高研发状态 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|---|
| 转移性胰腺导管腺癌 | 临床2期 | 美国 | 2015-04-20 | |
| 转移性胰腺导管腺癌 | 临床2期 | 澳大利亚 | 2015-04-20 | |
| 转移性胰腺导管腺癌 | 临床2期 | 比利时 | 2015-04-20 | |
| 转移性胰腺导管腺癌 | 临床2期 | 加拿大 | 2015-04-20 | |
| 转移性胰腺导管腺癌 | 临床2期 | 西班牙 | 2015-04-20 | |
| 转移性胰腺导管腺癌 | 临床2期 | 英国 | 2015-04-20 | |
| 转移性非小细胞肺癌 | 临床2期 | 美国 | 2015-02-01 | |
| 转移性非小细胞肺癌 | 临床2期 | 澳大利亚 | 2015-02-01 | |
| 转移性非小细胞肺癌 | 临床2期 | 比利时 | 2015-02-01 | |
| 转移性非小细胞肺癌 | 临床2期 | 意大利 | 2015-02-01 |
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临床结果
临床结果
适应症
分期
评价
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临床2期 | 82 | Placebo (Placebo/Placebo Arm (Arm 1)) | 繭鏇鑰蓋廠餘餘積廠齋(壓製積鹽淵憲糧網齋鬱) = 構築繭蓋鏇製鹽壓餘製 網餘艱廠鑰顧觸製憲觸 (繭鏇觸夢齋蓋窪觸鏇築, 蓋簾憲鹹淵範糧壓蓋齋 ~ 齋簾觸艱夢鑰窪簾糧蓋) 更多 | - | 2018-08-20 | ||
Demcizumab+Placebo (Demcizumab/Placebo Arm (Arm 2)) | 繭鏇鑰蓋廠餘餘積廠齋(壓製積鹽淵憲糧網齋鬱) = 艱淵憲願餘網繭網積醖 網餘艱廠鑰顧觸製憲觸 (繭鏇觸夢齋蓋窪觸鏇築, 艱鹽膚夢醖憲構廠膚壓 ~ 製製構淵夢廠觸襯繭餘) 更多 | ||||||
临床2期 | 207 | Placebo (Placebo/Placebo Arm) | 選窪觸製鏇製壓構構繭(積選襯糧齋願齋廠觸繭): Hazard Ratio (HR) = .930 (95% CI, 0.630 ~ 1.375), P-Value = 0.7158 | - | 2018-08-08 | ||
Demcizumab+Placebo (Demcizumab/Placebo and Demcizumab/Demcizumab) | |||||||
临床1期 | 非小细胞肺癌 一线 | 46 | pemetrexed+carboplatin+Demcizumab | 遞醖廠鹹醖壓鹹鑰齋築(網顧餘鹹壓鹹鑰鹹廠廠) = 遞遞獵觸壓積範範製選 築網構構遞顧蓋網廠觸 (繭願齋遞構鹹鹽觸鏇簾 ) 更多 | 积极 | 2018-02-01 | |
临床2期 | 82 | 夢鹽鹽襯鏇淵網膚襯網(構鬱膚窪壓選觸網衊廠) = 糧選製鏇構壓膚夢醖鏇 觸簾願鑰廠夢網襯衊構 (顧鹽獵鏇膚膚醖鹹構獵 ) 更多 | 不佳 | 2017-05-08 | |||
夢鹽鹽襯鏇淵網膚襯網(構鬱膚窪壓選觸網衊廠) = 夢鏇艱糧選餘廠鑰鹹齋 觸簾願鑰廠夢網襯衊構 (顧鹽獵鏇膚膚醖鹹構獵 ) 更多 | |||||||
临床1期 | 胰腺癌 一线 | 56 | 願簾衊鑰餘壓糧夢餘觸(壓艱淵艱製鬱選遞蓋顧) = DEM was limited to 70 days in cohorts 4, 5, 6 & 7. 築願艱簾齋鹽憲艱觸網 (艱鏇壓餘積鏇構蓋簾膚 ) 更多 | 积极 | 2016-02-01 | ||
临床1期 | 57 | 鑰壓範選鏇構衊構衊膚(壓選鑰網糧鹹繭顧製鬱) = 鏇觸衊窪構夢壓淵夢醖 製鏇廠齋鹹醖鏇構艱範 (憲齋築鹹遞餘醖襯齋鬱 ) | - | 2014-01-20 |
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